| Project/Area Number |
17H04209
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Hematology
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| Research Institution | Nagasaki University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
吉浦 孝一郎 長崎大学, 原爆後障害医療研究所, 教授 (00304931)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥15,470,000 (Direct Cost: ¥11,900,000、Indirect Cost: ¥3,570,000)
Fiscal Year 2019: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
Fiscal Year 2018: ¥5,980,000 (Direct Cost: ¥4,600,000、Indirect Cost: ¥1,380,000)
Fiscal Year 2017: ¥5,980,000 (Direct Cost: ¥4,600,000、Indirect Cost: ¥1,380,000)
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| Keywords | 骨髄異形成症候群 / ゲノム / 原爆被爆者 / 放射線 / 染色体 |
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| Outline of Final Research Achievements |
Ionizing radiation is a risk factor for myeloid neoplasms including myelodysplastic syndromes (MDS), and atomic bomb survivors have been shown to have a significantly higher risk of MDS. In this study, we performed genome analyses of MDS among survivors and found that proximally exposed patients had significantly fewer mutations in genes such as TET2 along the DNA methylation pathways, and they had a significantly higher rate of 11q deletions. Among the genes located in the deleted portion of chromosome 11, alterations of ATM was significantly more frequent in proximally exposed group with mutations identified on the remaining allele in two out of five cases. TP53, which is frequently mutated in therapy-related MDS, was equally affected between proximally and distally exposed patients. These results demonstrate that the genetic aberration profiles in MDS among atomic bomb survivors differed from those in therapy-related and de novo MDS.
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| Academic Significance and Societal Importance of the Research Achievements |
今回の研究では、原爆放射線によって誘発されたと考えられる骨髄異形成症候群(MDS)において、これまで報告されている初発MDSあるいは治療関連MDSとは異なる特徴を持つ細胞遺伝学的変異、およびゲノム変異の存在が示された。これは、加齢に伴うMDS発症（初発例）、化学療法/放射線治療によるMDS発症とは異なった経緯によって被爆者MDSが発症してきた可能性を示している。今後、さらに詳細なゲノム変異研究や症例の蓄積によってこれまで知られていなかったMDSの発症機構を明らかにできる可能性があり、悪性腫瘍の病態を考える上で有用な情報を提供できると考えられる。
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